LIQUID PREPARATIONS PART I Flashcards by Kim Grace

Liquid Preparations may be
dispensed in one of 3 ways

-original container
-Repacking a bulk product
-Compounding the solution, suspension or
emulsion in the dispensary

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Classification of Liquid Preparation

Solutions (single phase system)
Mixtures (two phase system)
Galenicals (extractives)
Sterile Products

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Oral solutions are ______________ mixtures of one or more solutes
dissolved in suitable solvent or mixture of
mutually miscible solvents

homogenous;

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These are homogenous mixtures of one or more solutes
dissolved in suitable solvent or mixture of
mutually miscible solvents

Oral solutions

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classified on the basis of physical
properties, method of preparation, use and
type of ingredients

Oral solutions

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Oral solutions areclassified on the basis of ________, _________, ________

classified on the basis of physical
properties, method of preparation, use and
type of ingredients

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Examples of oral solutions

Syrup, Elixir, Spirit, Aromatic water, tincture,
fluidextract

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ADVANTAGES OF SOLUTIONS AS AN ORAL DOSAGE FORM

-Liquids are easier to swallow than solids and
are therefore particularly acceptable for
pediatric and geriatric use
-A drug must usually be in solution before it can
be absorbed
-Solution is a homogenous system and
therefore the drug will be uniformly distributed
throughout the preparation

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DISADVANTAGES OF SOLUTIONS AS AN ORAL DOSAGE FORM

-Liquids are bulky and therefore inconvenient to transport and store
-Stability of ingredients in aqueous solution is often poorer than if
formulated as a tablet or capsule
-Solutions often provide suitable media for the growth of
microorganisms and may therefore require the incorporation of a
preservative
-Many liquid preparations are designed so that the normal dosage
of the drug is present in 5mL, or a multiple of 5 mL, of the product
-The taste of a drug, which is usually unpleasant, is always more
pronounced when in solution than in solid form

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The design and formulation of oral solutions involves the combination of ingredients with _____________
_________ to enhance the __________ of effectiveness of
the product

medicinal agents; acceptability

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Several considerations in the design and formulation of oral solutions:

-concentration of the drug
-solubility of the drug, selection of the liquid vehicle
-physical and chemical stability
-preservation of the
preparation
-appropriate excipients such as buffers,
solubilizers, sweetening agents, viscosity controlling
agents, color and flavors

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Successful design and formulation of liquids, as well as other dosage forms, requires both ________ and
______________ acuity

scientific and pharmaceutical acuity

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concentration of the
dissolved solute in a saturated solution

Solubility

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Is solubility qualitative or quantitative?

Quantitative

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drugs are present in solution at
_____________ concentrations, otherwise, the drug may
crystallize as a result of changes in temperature or by
“_____________” from other ingredients or particulate matter present

unsaturated; seeding

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Solubility is associated with the Effects of _________, effect of _____________, effect of
______________

pH, molecular structure, temperature

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process by which the apparent
solubility of a poorly water soluble substances
is increased

Solubilization

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Solubilization Techniques

addition of cosolvent, salt
formation, prodrug method, micellization

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Drug substances in general are __________ (more/less) stable in liquid media
than in the solid dosage form.

less stable

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consider both the pH solubility profile
and stability profile in order to select the optimum pH for
formulating the liquid oral dosage form

Chemical Stability

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involves the formation of precipitate, less
soluble polymorph, adsorption of the drug substances onto
container surfaces, microbial and product appearance

Physical Stability

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Solvent for aq solutions

Purified Water (water for injections)

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obtained by deionization,
distillation, ion exchange, reverse osmosis,
filtration or other suitable procedures

Water

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T/F: Although water is very widely used for inclusion in pharmaceutical preparations, it may not be possible to ensure complete solution of all ingredients at all normal storage temperatures.

Water for parenteral administration

Water for Injections, Bacteriostatic Water for Injections, or Sterile Water for Injections

The acceptability of the product is a ___________ evaluation and includes properties such as color, odor, taste and clarity

subjective

Major impurities in water are:

calcium, iron, magnesium, silica and sodium

Non-Aqueous solutions

- Fixed oils of vegetable origin - Alcohols - Polyhydric alcohols - Dimethylsulphoxide - Ethyl ether - Liquid paraffin

When mixed with water, a ____________ ___________ is formed capable of dissolving both alcohol-soluble and water-soluble substances, a feature especially useful for extraction and purification of active constituents from crude drugs and synthetic procedures

hydroalcoholic mixture;

Example of alcohols

Alcohol, diluted alcohol, rubbing alcohol, isopropyl rubbing alcohol

Second most commonly used solvent in pharmaceutical industry for many organic compounds

Alcohols

Recommended Alcohol content (OTC oral drugs) for children over 12 years of age and adults

10%

Recommended Alcohol content (OTC oral drugs) for children 6 to 12 years of age

Recommended Alcohol content (OTC oral drugs) for children under 6 years of age

0.5%

In topical preparations, glycerin is used for its ___________ and _________ properties

humectant; emollient

Glycerin is used in pharmaceutical formulations including:

oral, otic, ophthalmic, topical and parenteral preparations

Clear, syrupy liquid with a sweet taste and is miscible with water and alcohol

Glycerin

Viscous liquid and miscible with water and alcohol

Propylene Glycol

In oral preparations, glycerin is used as ________, ____________ agents, ___________________ and viscosity increasing agent

solvent; sweetening; antimicrobial preservatives;

Widely used as solvent, extractant, preservative in a variety of liquid pharmaceutical formulations including parenteral

Propylene Glycol

Often used in place of glycerin

Propylene Glycol

As an antiseptic it is similar to ethanol, and against molds it is similar to glycerin and only slightly less effective than ethano

Propylene Glycol

__________ is used as carrier for emulsifiers and as vehicle for flavors, as opposed to ____________, due to its lack of ____________

Propylene Glycol; ethanol; volatility

Miscellaneous Solvents

- Isopropyl myristate and isopropyl palmitate - Dimethylformamide and dimethylacetamide - Kerosene - Xylene - Glycofurol

Other Formulation Additives

- Buffers - Density modifiers - Isotonicity modifiers - Viscosity enhancement - Preservatives - Reducing agents and antioxidant - Sweetening agents - Flavors and perfumes - Colors

These are materials which, when dissolved in a solvent, will enable the solution to resist any change in pH should an acid or alkali be added

Buffers

Examples of buffers

Carbonates, citrates, gluconates, lactates, phosphates, tartrates

Most body fluids has a

pH of 7.4

Although buffers ensure pH stability, the buffer system can effect other properties such as

solubility and kinetics

Can act as general-acid or general-base catalysts and cause degradation of the drug substance

Buffers

pH and usual conc (%) of acetic acid and salt

ph 3.5-5.7, 1-2%

_________ strength contribution of the buffer systems can also effect stability.

Ionic

pH and usual conc (%) of Citric acid and a salt

2.5-6 pH; 1-3%

pH and usual conc (%) of Phosphoric acid salts

6-8.2 pH; 0.8-2%

Most widely used material for density modification is ____________

DEXTROSE

pH and usual conc (%) of Glutamic acid

8.2-10.2 pH; 1-2%

Solutions of lower density than cerebrospinal fluid will tend to ___________ after injection and those of higher density will _________

rise; fall

It is rarely necessary to control the density of solutions EXCEPT when formulating ___________

spinal anesthetics

Compounds contributing to the _____________ of a product reduce the pain of injection in areas with nerve ending

isotonicity

example of Viscosity Enhancement

Povidone, hydroxyethylcellulose, carbomer

alcohol content of __________% by weight in acid solutions and _____________% by weight, in alkaline solutions is sufficient to prevent microbial growth

15% by weight in acid solutions and 18% by weight, in alkaline solutions

may serve as tonicity contributors as well as stabilizers for pH

Buffers

examples of Isotonicity Modifiers other than buffers

Dextrose and NaCl

Propylene glycol is used as solvent in oral solution and topical preparations, and it can function as a preservatives in the range of ____________

15 to 30%

____________ concentrations of gelling agents can be used to increase the apparent viscosity of the product

low

alcohols used in lower concentrations (about 1%) as preservatives

Chlorobutanol and phenylethyl alcohol,

acid that has low solubility in water, inhibitory action varies from 0.1-0.5%, activity depends on the pH of the medium because only the undissociated acid has antimicrobial properties

Benzoic acid

useful as preservatives when it is used as solvent, however, it does need a relatively high concentration, somewhat greater than 15% to be effective

Ethanol

criteria for acceptability of preservatives

- safety and lack of toxicity after oral intake - must be soluble, stable and microbiologically active - compatible with the active ingredients as well as other components of the formulation

Optimum activity of Benzoic acid occurs at pH values below _________ and pH values above pH _______, benzoic acid is almost inactive

4.5; 5

Most alcohol containing preparations such as _________, ________, ___________ are self preserving and will not require preservation

elixirs, spirits, tinctures

esters of p-hydroxybenzoic acid and include methyl, ethyl, propyl, butyl derivatives

Parabens

When choosing a suitable preservative it must be ensured that: _____________ of the preservative onto the container from the product does not occur; and its efficiency is not impaired by the ___________ of the solution or by the interactions with other ingredients

adsorption; pH

Too ____________ concentration of alcohols may result in incompatibilities in suspension and emulsion system

high

Water solubility of the parabens _____________ as the molecular weight increases, from 0.25% for the methyl ester to 0.02% for the butyl ester

decreases

Esters are stable over a pH range _________

4-8

Has Broad spectrum of antimicrobial activity,and most effective against molds and yeasts

Esters

Antimicrobial activity _____________ as the chain length of the alkyl moiety is increased but aqueous solubility __________, therefore a mixture of parabens is frequently used to provide effective preservations

increases; decreases

Quarternary Ammonium Compounds Example

Benzalkonium Chloride

mixture consisting principally of homologs C12H25 and C14H29. This preservative is used at relatively low concentrations (0.002-0.02%)

Benzalkonium Chloride

Optimal activity of Quaternary Ammonium Compounds is met at pH ____________ and at _______ temperature

pH 4-10; Stable at room temperature

Used as external preservatives

Quarternary Ammonium Compounds

Antifungal Preservatives

Butyl parabens, methyl paraben, ethyl paraben, propyl paraben Benzoic acid, potassium sorbate Sodium benzoate, sodium propionate Sorbic acid

Antimicrobial Preservatives

Benzalkonium chloride, benzathonium chloride, benzyl alcohol, bronopo Centrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorcresol, creso Ethanol, glycerin, hexetidine, imidurea, phenol, phenoxyethanol, phenylmercuric nitrate Propylene glycol, thimerosa

Because of its cationic nature – it is incompatible with many anionic compounds such as surfactants and can bind to nonionic surfactants

Quarternary Ammonium Compounds

examples of reducing agents

sodium metabisulfite, or antioxidants such as butylated hydroxyanisole or butylated hydroxytoluene

Polyhydric alcohols examples

Maltilol, lactilol, isomalt, fructose, xylitol

For unit dose parenteral products, such as injections of nicotinamide and ascorbic acid, it is possible to use _____________ free from dissolved air and to replace the air in the headspace by nitrogen or another inert gases

Water for Injections

traditionally the most widely used sweetening agents

Low molecular weight carbohydrates, such as sucrose

has the advantage of being colorless, very soluble in water, stable over a pH range of about 4 – 8, and by increasing the viscosity of fluid preparations, will impart to them a pleasant texture in the mouth

Sucrose

The decomposition of pharmaceutical products by the oxidation can be controlled by the addition of ___________

reducing agents

also possess sweetening power and can be included in the preparations for diabetic use

Polyhydric alcohols

Sweetening agent with unpleasant aftertaste

Saccharin

Artificial sweetener examples

E954, E951, E950, E957, E952, E959

Most commonly used sweetening agent

Sucrose

Banned sweetening agent

Sodium cyclamate

T/F: The simple use of sweetening agents may not be sufficient to render palatable a product containing a drug with a particularly unpleasant taste

Sweetening agent that is not very stable in solution

aspartame

The inclusion of __________ has the additional advantage of enabling the easy identification of liquid products

flavors

Particularly useful in pediatric formulation to ensure patient compliance

Flavors and Perfumes

Suitable Masking Flavors for Salty

Apricot, butterscotch, liquorice, peach, vanilla, maple, wintergreen

Suitable Masking Flavors for Sour

Citrus fruits, liquorice, raspberry

Suitable Masking Flavors for Bitter

Anise, chocolate, mint, passion fruit, wild cherry

Suitable Masking Flavors for Sweet

Vanilla, fruits, berries

are pigments that are insoluble in water and which impart color by dispersing and reflecting light, they are not used for aqueous solutions

Lakes

are water soluble and exhibit color by transmitting light, should be used at the lowest possible concentration required to produce the desired color, higher concentration result in a dull color

Dyes

present in trace amounts

dyes

coloring agents that should be dissolved prior to mixing with the bulk of the formulations.

dye

LIQUID PREPARATIONS PART I Flashcards

(109 cards)